癌变·畸变·突变2026，Vol.38Issue(1)：7-14,8.DOI:10.3969/j.issn.1004-616x.2026.01.002
自噬在5-氟尿嘧啶联合奥沙利铂诱导结肠癌细胞铁死亡中的作用
Effect of autophagy on ferroptosis in colon cancer cells treated with the combination of 5-fluorouracil and oxaliplatin
摘要
Abstract
OBJECTIVE:To investigate the role of autophagy in inducing ferroptosis in human colon cancer SW620 cells treated with 5-fluorouracil(5-FU)combined with oxaliplatin(L-OHP).METHODS:The CCK-8 assay was used to assess the effects of different concentrations of 5-FU and L-OHP acting alone on SW620 cell proliferation after 24 h.The IC50 values for both drugs were calculated,and the IC50 concentrations were selected for subsequent combination treatment.SW620 cells were then divided into eight groups:control,5-FU,L-OHP,5-FU+L-OHP,autophagy inhibitor 3-methyladenine(3-MA),3-MA+5-FU,3-MA+L-OHP,and the triple combination of 3-MA,5-FU and L-OHP.Reagent kits were used to detect reactive oxygen species(ROS)and malondialdehyde(MDA)levels in each cell group.Western blot analysis was employed to assess the expression of ferroptosis-related proteins SLC7A11,GPX4,and ACSL4,as well as autophagy-related protein LC3B.Transmission electron microscopy was utilized to observe mitochondrial morphology.RESULTS:Compared with the control group,both 5-FU and L-OHP individually inhibited SW620 cell proliferation(P<0.01).The calculated IC50 values for cell survival under single treatment with 5-FU and L-OHP were 2 971 and 185 μmol/L,respectively.Combined treatment at the IC50 concentrations of both drugs further inhibited SW620 cell proliferation(P<0.01).Both single and combined treatments with 5-FU and L-OHP significantly increased ROS and MDA levels(P<0.01),while decreasing the ferroptosis-related proteins SLC7A11 and GPX4(P<0.01),and increased ACSL4 expression(P<0.05).Following intervention with the autophagy inhibitor 3-MA,compared to the control group,the triple combination group exhibited decreased expression of ferroptosis-related proteins SLC7A11 and GPX4(P<0.01)and increased ACSL4 expression(P<0.01).In the L-OHP-treated group and the 5-FU and L-OHP group,intracellular autophagy-related protein LC3B-Ⅱ/Ⅰ expression was upregulated(P<0.05 or P<0.01).Compared with the 5-FU and/or L-OHP groups,the triple-drug combination group exhibited further reduced cell viability(P<0.01)and significantly elevated MDA and ROS levels(P<0.01).In the 5-FU and/or L-OHP intervention groups supplemented with 3-MA,ACSL4 protein expression increased(P<0.05 or P<0.01),while SLC7A11 and GPX4 proteins expression decreased(P<0.05 or P<0.01).Transmission electron microscopy revealed that 5-FU and/or L-OHP induced mitochondrial damage in SW620 cells,with more pronounced morphological alterations observed in the combination treatment group.CONCLUSION:5-FU and L-OHP inhibited proliferation of SW620 colon cancer cells and induced ferroptosis.Co-treatment further enhanced the level of ferroptosis in cancer cells.Inhibition of autophagy potentiated the effect of combined 5-FU and L-OHP treatment.关键词
结直肠癌/自噬/铁死亡/奥沙利铂/5-氟尿嘧啶Key words
colorectal cancer/autophagy/ferroptosis/oxaliplatin/5-fluorouracil分类
医药卫生引用本文复制引用
吉佳音,罗梦雨,李红霞,钟照玥,康玲..自噬在5-氟尿嘧啶联合奥沙利铂诱导结肠癌细胞铁死亡中的作用[J].癌变·畸变·突变,2026,38(1):7-14,8.基金项目
塔里木大学校长基金(TDZKSS202311) （TDZKSS202311）
